Conventionally the L-amino acids have been industrially produced by method of fermentation utilizing strains of microorganisms obtained from natural sources or mutant of the same especially modified to enhance L-amino acid productivity.
There have been disclosed many techniques to enhance L-amino acid productivity, for example, by transformation of microorganism by recombinant DNA (see, for example, U.S. Pat. No. 4,278,765). These techniques based on the increasing of activities of the enzymes involved into amino acid biosynthesis and/or desensitizing the target enzymes to the feedback inhibition by produced L-amino acid (see, for example, Japanese Laid-open application No 56-18596 (1981), WO 95/16042 or U.S. Pat. Nos. 5,661,012 and 6,040,160).
On the other hand, increased L-amino acid excretion can enhance the productivity of strain producing L-amino acid. Strain of bacterium belonging to the genus Corynebacterium having increased expression of L-lysine excretion gene (lysE gene) is disclosed (WO 9723597A2). In addition, genes coding for the efflux proteins suitable for secretion of L-cysteine, L-cystine, N-acetylserine or thiazolidine derivatives are also disclosed (U.S. Pat. No. 5,972,663).
At present several Eseherichia coli genes coding for putative membrane proteins enhancing L-amino acid production are disclosed. Additional copy of rhtB gene makes a bacterium more resistant to L-homoserine and enhances production of L-homoserine, L-threonine, L-aianine, L-valine and L-isoleucinc (European patent application EP994 1 90A2). Additional copy of rhtC gene makes a bacterium more resistant to L-homoserine and L-threonine and enhances production of L-homoserine, L-threonine and L-leucine (European patent application EP1013765A1). Additional copy of yahN yeaS, yfiK and yggA genes enhance production of L-glutamic acid, L-lysine, L-threonine L-alanine, L-histidine, Lproline, L-arginine, L-valine and L-isoleucine (European patent application EP1016710A2). And though complete genome sequence of Eseheriehia coli strain K-12 is described (Blattner F. R., Plunkeft G., Bloch C. A. et al., Science, 227, 1453-1474, 1997;there are many OREs, the function of which still remains unknown.